What Is Particle Analysis?
Particle analysis is the separation and extraction of particles in a sample, and some methods also allow for image analysis. Generally, particle size distributions are obtained, and in image analysis, images are statistically processed by measuring area, perimeter, and diameter, and analyzing circularity and aspect ratio. Analysis of particle size and shape is useful for particle characterization and evaluation. The methods used are:
- Electron microscopy (SEM/TEM)
- Laser diffraction/scattering (LD)
- Dynamic light scattering (DLS)
- Small-angle X-ray scattering (SAXS)
Depending on the state of the sample to be analyzed and the purpose of the analysis, one or a combination of the above methods will be used. Since the information that can be obtained depends on the analysis method, it is necessary to select the method that best suits the purpose of the analysis.
Method and Procedure for Particle Analysis
When acquiring information through particle analysis, it is necessary to follow the appropriate procedures for each method used in order to obtain accurate data. This section describes the procedure for particle analysis using electron microscopy, which is a typical method.
Sample Preparation
When performing particle analysis, prepare a sample to obtain an image for analysis. The method of particle analysis varies depending on the type and format of the sample, so use a sample appropriate for the tools used and the data required. For example, when analyzing by dynamic light scattering (DLS), the sample must be dispersed in a solvent. In contrast, when using methods such as laser diffraction and scattering, it is possible to analyze dry powders, dispersions, and particles in aerosols.
SEM/TEM Image Acquisition
Next, obtain SEM or TEM images. A scanning electron microscope produces an SEM image, while a transmission electron microscope produces a TEM image. The SEM image does not show the inside, but it produces a three-dimensional image that is close to the human senses. On the other hand, the TEM image requires knowledge to understand the structure, but it provides a circular plan view, allowing analysis of the internal structure. Data that can be analyzed varies depending on the type of image, so use SEM images for accurate determination of the overall shape and TEM images for high-magnification images of the internal structure.
SEM/TEM Image Processing
Having obtained an image for particle analysis, the next step is to improve the image quality by removing noise, enhancing contrast, and correcting image distortion. Once a clear SEM/TEM image is obtained by modifying the sample, the particle images are further separated from the background so that the overlapping particle images can be recognized as separate particles. After these image processing steps, analyses such as particle size measurement and distribution state measurement can finally be performed.
SEM/TEM Image Analysis
Once the images are processed and ready for analysis, particle size and shape characteristics are quantified. During analysis, the information in the SEM/TEM image, which is originally a monochrome image, may be colorized to make it easier to understand, or several TEM images, which are originally planar, may be combined to create a three-dimensional image. Systems have been developed that can almost automatically acquire and process SEM/TEM images, as well as perform basic analysis, so use them as needed.
Particle Analysis Methods Other than Electron Microscopy
In addition to the electron microscopy analysis described above, there are a variety of particle analysis methods that can be used depending on the type of sample and purpose of the analysis. This section summarizes the outline and features of particle analysis methods using techniques other than electron microscopy.
Laser Diffraction/Scattering
Laser diffraction/scattering is a method to determine the particle size distribution by irradiating the particles to be analyzed with a laser beam and observing the diffracted and scattered light emitted by the irradiation. Diffracted and scattered light is the light emitted in various directions (forward and backward, up and down, left and right) when the particles are irradiated with a laser beam. The constant spatial pattern formed by this light is called the light intensity distribution pattern. Since the light intensity distribution pattern changes into various shapes depending on the size of the particles, calculations are performed based on this pattern to obtain the particle size distribution for particle analysis.
Dynamic Light Scattering
Particles dispersed in a liquid randomly diffuse in different directions. Brownian motion is the motion caused by particles colliding with solvent molecules, which transfers energy and induces particle diffusion. Dynamic light scattering is an analysis method that uses Brownian motion of particles dispersed in a liquid. This method takes advantage of the fact that smaller particles, which are more susceptible to energy changes, diffuse faster than larger particles, and determines the particle size from their diffusion velocity.
Small-Angle X-ray Scattering
Small-angle X-ray scattering is an analytical method that measures the intensity of X-rays scattered by a sample as a function of the scattering angle. Because it can analyze samples other than solution media, it is used for samples that cannot be analyzed by dynamic light scattering, such as particles in a gel or a high-viscosity liquid, because they do not easily or not at all exhibit Brownian motion. Another difference from dynamic light scattering is that it is less susceptible to coarse particles, is not affected by optical activity due to visible light, and can be easily applied to colored samples.
Size Exclusion Chromatography (SEC)
Size exclusion Chromatography (SEC) is an analytical method that evaluates the physical properties of synthetic polymers such as plastics, copolymers and oligomers, and natural and biological polymers such as cellulose, proteins, and antibody drugs in solution, based on their molecular weight and structure. If the sample to be analyzed is a polymer, the results of the analysis will have a significant bearing on mechanical strength, tensile strength, and impact resistance. For biopolymers such as proteins and antibodies, molecular weight information can determine whether the polymer is a monomer or a multimer, which helps optimize operations such as purification and separation.
Applications of Particle Analysis
Particle analysis has found applications in a variety of fields in recent years and is used in familiar places. Here are some examples of how particle analysis has been applied to various fields of everyday use.
Pharmaceutical Analysis
Biopharmaceutical formulation requires adequate characterization of the ingredients. Accurate and reproducible results allow for monitoring and optimization of the formulation. Particle classification also provides essential information about the quality of the drug product. In addition, it is very important to analyze the structure and design of particles, which are the building blocks for the development of user-friendly drugs, such as those that are easy to take and absorb in the body.
Production of Lithium-ion Batteries
All-solid-state lithium-ion batteries are made from nonflammable solids, making them safer than conventional batteries, and are expected to have a larger capacity. Among them, those called bulk-type all-solid-state batteries consist of a cathode active material, a solid electrolyte, and an anode active material made of fine particles processed from raw material particles. Therefore, it is important to accurately evaluate raw materials particles and processed fine particles. Analysis of these particles should be performed with minimal influence of moisture. Laser microscopy allows observation and analysis of particles without the use of water or organic solvents.
Quality Control in Plants
In recent years, the density of components that make up a product has increased in the manufacturing industry, and the standards for reliability have become more stringent every year. Therefore, particle analysis is used as a method to determine defects and failures of products in plants. Particle analysis using an electron microscope can accurately determine minute defects and deviations from specifications. The results of analysis by energy-dispersive X-ray spectroscopy and observation by electron microscopy can be displayed together, providing insight into the composition of defective areas.
Cleanliness Control in Cleanrooms
Scanning electron microscopy and energy-dispersive X-ray spectroscopy can be used for cleanliness control to determine the chemical composition of individual particles contained in a cleanroom. This allows producers to set individual cleanliness levels for particles that are harmful to the component, and to relax restrictions for particles that have less impact. Thus, using molecular analysis for cleanliness control can simplify analysis by distinguishing between particles that should be removed and those that should not, thereby greatly reducing production time.
*Images shown are for illustrative purposes only.
History of Particle Analysis
Particle analysis has evolved in response to the needs of a period of economic growth. This is supported by the theory that in the 1970s, particle size analyzers were developed using lasers, the most advanced technology of the time. This method, which can intuitively determine the shape and distribution of particles from images, has been widely recognized and actively used since the invention of the optical microscope. However, it is also a very laborious and time-consuming method for analyzing a large number of particles and its use has been limited. In recent years, digital imaging technology and the development of analysis software have made image analysis more realistic, and the number of situations in which it is used has been increasing.
Latest Trends in Particle Analysis
Although particle analysis is not a method with a long history, the technology has been advancing very rapidly in the last 30 years. For example, electron microscopes can be automated and display real-time 3D images. Software development has also led to the automation of image processing and analysis. In recent years, particle analysis software that runs on a standard PC equipped and graphics card is available, and the use of AI is also progressing. In addition, particle analysis technology is required in an increasing number of situations in proportion to technological advances, and there is no doubt that its importance will grow in the future. Although many of the instruments used for analysis are still expensive, it is expected to improve in the future as technology develops and becomes more widespread.
Yokogawa’s FlowCam: Flow Imaging Microscope Series for Particle Analysis
Yokogawa's FlowCam, flow imaging microscope series is an instrument and solution for efficient particle analysis. It combines the benefits of digital imaging, flow cytometry, and microscopy in a single instrument. Counting and analyzing tens of thousands of particles per minute, it can measure and analyze particles that cannot be observed by the naked eye with high image quality. It can be used in a wide range of industries, including characterization of algae and cyanobacteria in drinking water, identification of protein aggregates and foreign substances in biopharmaceuticals, the shape and size of printer toners, and the analysis of food and beverage products.
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